The effect of initial therapy with the fixed-dose combination of sitagliptin and metformin compared with metformin monotherapy in patients with type 2 diabetes mellitus

C. Reasner, L. Olansky, T. L. Seck, D. E. Williams-Herman, M. Chen, L. Terranella, A. O. Johnson-Levonas, K. D. Kaufman, B. J. Goldstein

Research output: Contribution to journalArticle

68 Scopus citations


Aims: This study was conducted to compare the glycaemic efficacy and safety of initial combination therapy with the fixed-dose combination of sitagliptin and metformin versus metformin monotherapy in drug-naive patients with type 2 diabetes. Methods: This double-blind study (18-week Phase A and 26-week Phase B) randomized 1250 drug-naÏve patients with type 2 diabetes [mean baseline haemoglobin A1c (HbA1c) 9.9%] to sitagliptin/metformin 50/500 mg bid or metformin 500 mg bid (uptitrated over 4 weeks to achieve maximum doses of sitagliptin/metformin 50/1000 mg bid or metformin 1000 bid). Results of the primary efficacy endpoint (mean HbA1c reductions from baseline at the end of Phase A) are reported herein. Results: At week 18, mean change from baseline HbA1c was -2.4% for sitagliptin/metformin FDC and -1.8% for metformin monotherapy (p < 0.001); more patients treated with sitagliptin/metformin FDC had an HbA1c value <7% (p < 0.001) versus metformin monotherapy. Changes in fasting plasma glucose were significantly greater with sitagliptin/metformin FDC (-3.8 mmol/l) versus metformin monotherapy (-3.0 mmol/l; p < 0.001). Homeostasis model assessment of β-cell function (HOMA-β) and fasting proinsulin/insulin ratio were significantly improved with sitagliptin/metformin FDC versus metformin monotherapy. Baseline body weight was reduced by 1.6 kg in each group. Both treatments were generally well tolerated with a low and similar incidence of hypoglycaemia. Abdominal pain (1.1 and 3.9%; p = 0.002) and diarrhoea (12.0 and 16.6%; p = 0.021) occurred significantly less with sitagliptin/metformin FDC versus metformin monotherapy; the incidence of nausea and vomiting was similar in both groups. Conclusion: Compared with metformin monotherapy, initial treatment with sitagliptin/metformin FDC provided superior glycaemic improvement with a similar degree of weight loss and lower incidences of abdominal pain and diarrhoea.

Original languageEnglish (US)
Pages (from-to)644-652
Number of pages9
JournalDiabetes, Obesity and Metabolism
Issue number7
StatePublished - Jul 2011



  • Diabetes
  • GIP
  • GLP-1
  • Metformin
  • Sitagliptin
  • Type 2 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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